A Phase II Study of IRD (Ixazomib, Lenalidomide, & Dexamethasone) for Consolidation Therapy Post Autologous Stem Cell Transplantation Followed by Maintenance Ixazomib or Lenalidomide for Multiple Myeloma
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 236
- 试验地点
- 10
- 主要终点
- Number of Participants With Improvement in Minimal Residual Disease (MRD)
研究概览
简要总结
The purpose of this research study is to evaluate a treatment regimen called IRD which will be given to participants after their stem cell transplant in an effort to help prolong the amount of time the participants are disease-free after transplant. IRD is a three-drug regimen consisting of ixazomib, lenalidomide (also called Revlimid), and dexamethasone. After 4 cycles of IRD, the participants will be randomized to receive maintenance therapy either with ixazomib or lenalidomide.
详细描述
Based on the further need to improve progression-free survival and overall survival post-autologous stem cell transplantation (ASCT) for multiple myeloma and the benefits seen of consolidation/maintenance treatment with immunomodulatory drugs thalidomide and lenalidomide and the proteasome inhibitor bortezomib, the natural next step is to evaluate combination regimens of immunomodulatory drugs and proteasome inhibitors as consolidation/maintenance post-ASCT. The regimen consisting of ixazomib, lenalidomide, and dexamethasone (IRD) has been shown to have low toxicity, and the availability of an oral formulation of ixazomib allows for easier administration when compared to bortezomib.
In this study, following consolidation with IRD, patients will be randomized to maintenance therapy with lenalidomide or ixazomib in order to collect pilot data comparing the toxicity and efficacy of maintenance therapy with immunomodulatory drugs and proteasome inhibitors.
09/23/2019: Upon review of the interim analysis, there will be no further randomizations into the maintenance portion of the trial. All patients will be enrolled into the lenalidomide arm with the exception of those who discontinue lenalidomide during the consolidation phase due to toxicity. Patients who discontinue lenalidomide may be enrolled into the ixazomib arm following approval from the principal investigator.
09/30/2021: Following analysis 4 in 2021, analysis of the primary endpoint, all patients receiving lenalidomide maintenance will be transitioned off-study. Patients receiving ixazomib may remain on trial until disease progression or unacceptable toxicity at the discretion of the treating physician and the site principal investigator.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Consolidation: Ixazomib, Lenalidomide, & Dexamethasone
Consolidation therapy will begin between Day 80 and Day 120 following ASCT and will consist of four 28-day cycles of IRD (ixazomib, lenalidomide, & dexamethasone). Barring dose modifications for toxicity, 4 mg of ixazomib and 40 mg of dexamethasone will be administered on Days 1, 8, and 15, and 15 mg of lenalidomide will be administered on daily on Days 1-21.
干预措施: Ixazomib (Biological)
Consolidation: Ixazomib, Lenalidomide, & Dexamethasone
Consolidation therapy will begin between Day 80 and Day 120 following ASCT and will consist of four 28-day cycles of IRD (ixazomib, lenalidomide, & dexamethasone). Barring dose modifications for toxicity, 4 mg of ixazomib and 40 mg of dexamethasone will be administered on Days 1, 8, and 15, and 15 mg of lenalidomide will be administered on daily on Days 1-21.
干预措施: Lenalidomide (Drug)
Consolidation: Ixazomib, Lenalidomide, & Dexamethasone
Consolidation therapy will begin between Day 80 and Day 120 following ASCT and will consist of four 28-day cycles of IRD (ixazomib, lenalidomide, & dexamethasone). Barring dose modifications for toxicity, 4 mg of ixazomib and 40 mg of dexamethasone will be administered on Days 1, 8, and 15, and 15 mg of lenalidomide will be administered on daily on Days 1-21.
干预措施: Dexamethasone (Drug)
Maintenance Arm 1: Ixazomib
Ixazomib will be administered on Days 1, 8, and 15 of a 28-day cycle at a starting dose of 4 mg until patient progresses or experiences an unacceptable toxicity.
干预措施: Ixazomib (Biological)
Maintenance Arm 2: Lenalidomide
Lenalidomide will be administered daily continuously for a 28-day cycle at a starting dose of 10 mg. If lenalidomide is tolerated well (i.e. no dose modification required) during the first three cycles, lenalidomide dose will be increased to 15 mg daily and will continue until patient progresses or experiences an unacceptable toxicity.
干预措施: Lenalidomide (Drug)
结局指标
主要结局
Number of Participants With Improvement in Minimal Residual Disease (MRD)
时间窗: After 4 cycles of IRD consolidation treatment (approximately Day 112 of consolidation treatment)
For the purposes of this study, a patient will be considered as having minimal residual disease if a positive result (1x10E06) is obtained using the Adaptive Clonoseq MRD testing.
次要结局
- Compare Toxicity Between the Two Maintenance Arms(30 days after the completion of maintenance treatment (estimated to be Day 1125 of maintenance treatment))
- Compare Response Rate Between the Two Maintenance Arms(Through completion of maintenance treatment (estimated to be day 1095 of maintenance treatment))
- Association of Overall Survival With MRD-positivity(Up to 18 months after completion of maintenance therapy (Up to 5 years after starting the study))
- Toxicity of IRD Consolidation(After 4 cycles of IRD consolidation treatment (approximately Day 112 of consolidation treatment))
- Response Rate of IRD Consolidation(After 4 cycles of IRD consolidation treatment (approximately Day 112 of consolidation treatment))
- Overall Survival of IRD Consolidation(Up to 18 months after completion of maintenance therapy (Up to 5 years after starting the study))
- MRD-negative Rate After ASCT(Prior to beginning consolidation treatment (Day -28 to Day 0))
- Association of Progression-free Survival With MRD-negativity(Up to 18 months after completion of maintenance therapy (Up to 5 years after starting the study))
- Association of Progression-free Survival With MRD-positivity(Up to 18 months after completion of maintenance therapy (Up to 5 years after starting the study))
- Progression-free Survival of IRD Consolidation(Up to 18 months after completion of maintenance therapy (Up to 5 years after starting the study))
- Compare Progression-free Survival Between the Two Maintenance Arms(Up to 18 months after completion of maintenance therapy (Up to 5 years after starting the study))
- Compare Overall Survival Between the Two Maintenance Arms(Up to 18 months after completion of maintenance therapy (Up to 5 years after starting the study))
- Rate of MRD-positive to MRD-negative Conversion Between the Two Maintenance Arms(Cycle 13 Day 1 of maintenance treatment (Approximately Day 364 of maintenance treatment))
- Association of Overall Survival With MRD-negativity(Up to 18 months after completion of maintenance therapy (Up to 5 years after starting the study))